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简介:AbstractToinvestigatetheroleofCD4^+helperT(Th)cellsinthememoryCTL-mediatedanti-tumorimmunity,theRAG-1geneknockoutmicewereadoptivelytransferredwithOT-1cellstogeneratethememoryCTL,theC57B1/6miceimmunizedwiththeepitopepeptideofOVAspecificThcellsandwithdifferentadjuvantswereadopfivelytransferredwiththesememory-CTLs,andthentheanimalswerechallengedwithtumorcellsEGT.ItwasfoundthatalthoughthesimpleimmunizationofmicewiththeepitopepeptideoftheOVAspecificThcellscouldgeneratemoreeffectCTL,butthiseffectwasnotsostrongenoughtoresistcompletelythechallengeswithtumorcells.Nevertheless,thememoryCTL-mediatedanti-tumorimmuneeffectrequiredthehelpsofTh1andTh2cells.Thecross-regulationbetweenThlandTh2cellsseemedtobebeneficialforthehosttogeneratemoreeffectorCTLformountinganefficientanti-tumorresponse.ItconcludedthattheinteractionbetweenThlandTh2cellsmightbemoreimportantthanthesinglesubsetofThcellsinthememoryCTL-mediatedanti-tumorimmuneresponse.Moreattentionshouldbepaidinthisregardforthefuturestudies.
简介:Wehaveconfirmedefficientanti-tumoractivitiesoftheperipherallymphocytestransducedwithap185HER2-specificchimericT-cellreceptorgenebothinmurineandinhumaninourpreviousstudies.TofurthertestthefeasibilityofchimericT-cellreceptorinabonemarrowtransplantationmodel,wefirst,madetwomurinetumorcelllines:MT901andMCA-205,toexpresshumanp185HER2byretroviralgenetransduction.MurinebonemarrowcellswereretrovirallytransducedtoexpressthechimericT-cellreceptorandgene-modifiedbonemarrowcellsweretransplantedintolethallyirradiatedmouse.Sixmonthsposttransplantation,p185HER2-positivetumorcells:MT-901/HER2orMCA-205/HER2wassubcutaneouslyorintravenouslyinjectedtomakemousemodelssimulatingprimarybreastcancerorpulmonarymetastasis.Theinvivoanti-tumoreffectsweremonitoredbythesizeofthesubcutaneoustumororcountingthetumornodulesinthelungsafterIndiainkstaining.ThesizeofthesubcutaneoustumorwassignificantlyinhibitedandthenumberofpulmonarynodulesweresignificantlydecreasedinmouserecipientstransplantedwithchimericT-cellreceptormodifiedbonemarrowcellscomparedwiththecontrolgroup.Ourresultssuggesttheefficientinvivoanti-tumoractivitiesofchimericT-cellreceptorgenemodifiedbonemarrowcells.